News

The Cancer Lottery

Monday, December 12, 2016

This is an excerpt of a feature that appreared in MIT Technology Review. Read the full article here.

Photo of Dr VarmusDr. Harold Varmus Photo credit: Matthew Septimus/Memorial Sloan Kettering Cancer Center Ever since the Human Genome Project, scientists have dreamed of using precise, personal molecular information to guide the diagnosis and treatment of human disease. The vision is simple: knowing the DNA sequence of people with particular diseases should reveal the mutations producing those illnesses and offer enticing targets for drugs designed to attack them. Unfortunately, biological complexity still far exceeds medical knowledge. Though researchers hoped that a limited number of common mutations would explain a broad swath of human illness—heart disease, high blood pressure, diabetes, schizophrenia—that has largely failed to hold true.

Cancer treatment is a bright spot in this disappointing story, however. Tumors typically do display genetic aberrations that offer potential targets for drugs. Long before there was widespread talk about precision oncology, targeted therapy had become a major player in cancer clinics. In 1998, the Food and Drug Administration approved a drug for a subset of breast cancer patients whose tumor cells displayed a particularly hyperactive version of a surface molecule known as the HER-2 receptor. Herceptin was the first targeted cancer treatment, and it was joined by two other blockbuster drugs, Gleevec (which targeted a mutation in a form of leukemia) in 2001 and Zelboraf (which targeted a mutation in melanoma) in 2011.

The success of these drugs gave rise to the hope that with DNA sequencing becoming relatively cheap and accessible, the genome of any tumor could be mined for clues about how to directly attack its specific mutations. That, in a nutshell, is the animating idea behind precision oncology: doctors could biopsy a tumor, analyze its DNA sequence, and identify mutations—some of which would render the cancer vulnerable to already approved molecular medicines. Where doctors once struggled to treat “breast cancer” or “skin cancer,” the mutation, not the tissue of origin, would become the disease’s fundamental defining characteristic.

It sounds almost irresistible. But researchers who hoped to find that every cancer has a genetic Achilles’ heel have discovered that the biology of cancer mutations is far more complicated. 

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Not every cancer center is positioned to take advantage of the latest advances in tumor genomics—an inequity recently acknowledged by officials of President Obama’s Cancer Moonshot project. “The vast majority of Americans do not have easy access to precision cancer testing,” they noted in a report issued in September, “since oncology clinical trials are offered mainly at large academic cancer centers and not at community cancer centers where most cancer patients receive their treatments.”

Indeed, sequencing of tumors remains a relatively uncommon practice. Harold Varmus, a former NIH director and now a professor at Weill Cornell Medical College, says one of the big “lost opportunities” in cancer genomics is how few patients are having it done. Medicare does not cover this type of DNA sequencing, and neither do most health insurers. The cost is not insignificant: tumor sequencing can run from $600 to $1,000 per biopsy, depending on who is doing it. But Varmus points out that it’s already cheaper than some standard features of cancer care, such as multiple imaging tests. “These cancer patients end up having dozens of imaging scans—CT scans, PET scans, MRIs,” he says. Each of those tests typically costs $500 to $5,000."

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